Chemical Analysis of the Ingredients of 20% Aqueous Ethanol Extract of Nardostachys jatamansi through Phytochemical Study and Evaluation of Anti-Neuroinflammatory Component.

Hyuncheol Oh,Chi-Su Yoon,Kwan-Woo Kim,Youn-Chul Kim,Maria Ferraro,Sung-Joo Park,Dong-Gu Kim,Gi-Sang Bae

doi:10.1155/2021/5901653

Abstract

Nardostachys spp. have been widely used in Asia as a folk medicine. In particular, the extracts of Nardostachys jatamansi, a species that grows in China, India, and Tibet, have been used to treat mental disorders, hyperlipidemia, hypertension, and convulsions. In this investigation, the potential of 20% aqueous ethanol extract of N. jatamansi (NJ20) as a botanical drug was explored by chemically investigating its constituents and its anti-neuroinflammatory effects on lipopolysaccharide- (LPS-) induced in vitro and in vivo models. Nine secondary metabolites were isolated and identified from NJ20, and quantitative analysis of these metabolites revealed desoxo-narchinol A as the major constituent. In LPS-challenged cells, pretreatment with NJ20 inhibited the LPS-induced excessive production of proinflammatory mediators, such as nitric oxide, prostaglandin E2, interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α. NJ20 also attenuated the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2. Additionally, pre-intraperitoneal injection of NJ20 downregulated the mRNA overexpression of IL-1β, IL-6, and iNOS in the prefrontal cortex, hypothalamus, and hippocampus of the LPS-stimulated C57BL/c mouse model. Chemical and biological investigations of NJ20 revealed that it is a potential inhibitor of LPS-induced neuroinflammatory responses in microglial cells and mouse models. The major active constituent of NJ20, desoxo-narchinol A, demonstrated anti-neuroinflammatory effects. Hence, our findings indicate that NJ20 may be a promising herbal mixture for developing a functional product and/or herbal drug for treating neuroinflammatory diseases.

Highlights

Microglial cells are important immune cells of the central nervous system (CNS) [1]. ese cells are activated in response to brain injury, immunological stimuli, infection, and stress to sustain neuronal homeostasis
Recently, an optimized High-performance liquid chromatography (HPLC)-UV method for the quantitative analysis of sesquiterpenes in Nardostachys Radix et Rhizoma, including optimized sample preparation conditions, was reported. Results of this method suggested that 20% (v/v) aqueous EtOH extract of N. jatamansi contained the highest amount of desoxo-narchinol A among the extracts analyzed [23]
Nine metabolites from NJ20 were identified as 8α–hydroxypinoresinol (1) [16], desoxo-narchinol A (2) [13], pinoresinol (3) [24], nardosinonediol (4) [25], kanshone A (5) [25], isonardosinone (6) [11], deblion (7) [25], 1α-hydroxy-(-)-aristolone (8) [26], and nardoaristolone B (9) [12], by comparing their retention time in HPLC chromatograms and their corresponding structures determined using nuclear magnetic resonance (NMR) spectroscopy with previous findings (Figures 1 and 2). e quantitative analysis of compounds 1–9 in NJ20 was performed by HPLC. e contents of each compound in the extract were calculated from the peak areas by interpolation to standard calibration curves (Table 1)

Summary

Introduction

Microglial cells are important immune cells of the central nervous system (CNS) [1]. ese cells are activated in response to brain injury, immunological stimuli, infection, and stress to sustain neuronal homeostasis. Another report has demonstrated that the N. jatamansi extract increases insulin sensitivity in the skeletal muscles and suppresses glucose production in the liver, helping control hyperglycemia [3]. In another investigation, the water extract of N. jatamansi inhibited lipopolysaccharide- (LPS-) induced endotoxin shock by reducing proinflammatory cytokines via the inhibition of the mitogenactivated protein kinase (MAPK) pathways [9]. We reported the isolation of different components from the rhizomes and roots of N. jatamansi, including desoxo-narchinol A, narchinol B, nardosinone, isonardosinone, kanshone E, and kanshone B, as well as the beneficial effects of these compounds against LPS-induced neuroinflammation in BV2 microglial cells [10,11,12,13]. In the course of our continuous study on the bioactive components from N. jatamansi, C12-nardosinone type sesquiterpenoids, such as narchinol B and desoxonarchinol A, were demonstrated to be the most potent antineuroinflammatory components in BV2 and primary microglial cells [10, 13]

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